Communications
Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201602790
German Edition:
DOI: 10.1002/ange.201602790
P4 Functionalization
Direct Synthesis of Phospholyl Lithium from White Phosphorus
Ling Xu, Yue Chi, Shanshan Du, Wen-Xiong Zhang,* and Zhenfeng Xi
Dedicated to Professor Li-Cheng Song on the occasion of his 80th birthday
Abstract: The selective construction of P¢C bonds directly
from P4 and nucleophiles is an ideal and step-economical
approach to utilizing elemental P4 for the straightforward
synthesis of organophosphorus compounds. In this work,
a highly efficient one-pot reaction between P4 and 1,4-dilithio1,3-butadienes was realized, which quantitatively affords
phospholyl lithium derivatives. DFT calculations indicate
that the mechanism is significantly different from that of the
well-known stepwise cleavage of P¢P bond in P4 activation.
Instead, a cooperative nucleophilic attack of two Csp2 Li bonds
on P4, leading to simultaneous cleavage of two P¢P bonds, is
favorable. This mechanistic information offers a new view on
the mechanism of P4 activation, as well as a reasonable
explanation for the excellent yields and selectivity. This method
could prove to be a useful route to P4 activation and the
subsequent production of organophosphorus compounds.
Organophosphorus compounds have been widely used as
agrochemicals, detergents, and flame retardants.[1] They can
also serve as versatile ligands in coordination chemistry,
organometallic chemistry, and metal-mediated organic synthesis. Generally, the vast majority of phosphorus atoms in
organophosphorus compounds are derived from white phosphorus (P4).[2] However, multistep and environmentally toxic
processes are usually involved to make organophosphorus
compounds from elemental P4, either via phosphorus halides
(such as PCl3, PCl5, Scheme 1 a) or via the extremely toxic
phosphine (PH3) gas (Scheme 1 b). Although metal-mediated
P4 activation to construct P¢C bonds is a promising strategy
because it releases far less pollution (Scheme 1 c), it generally
suffers from very low reaction selectivity between the formed
LnM-[Px] (x Š 2)[3, 4] and organic reagents.[5] To make this
promising approach practical, the following two problems
should be overcome: 1) the activated P atoms in the [Px]
moiety may act as nucleophilic sites, which leads to poor
regioselectivity with organic substrates, and 2) the reactivity
[*] Dr. L. Xu, Y. Chi, S. Du, Prof. Dr. W.-X. Zhang, Prof. Dr. Z. Xi
Beijing National Laboratory for Molecular Sciences (BNLMS)
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University
Beijing 100871 (China)
E-mail: [email protected]
Prof. Dr. W.-X. Zhang
State Key Laboratory of Elemento-Organic Chemistry
Nankai University,Tianjin 300071 (P.R. China)
Supporting information for this article (including experimental
details, X-ray crystallographic data, and scanned NMR spectra of all
new products) can be found under:
http://dx.doi.org/10.1002/anie.201602790.
Angew. Chem. Int. Ed. 2016, 55, 9187 –9190
Scheme 1. Construction of P¢C bonds.
difference among the P¢P bonds in the [Px] moiety is small.
From the view point of sustainability and green chemistry, the
direct and highly efficient construction of P¢C bonds from P4
and organic or organometallic substrates is an ideal process
(Scheme 1 d).
Generally, the reaction between simple organomonolithium reagents and P4 affords a complicated mixture,
whatever the molar ratio of organolithium reagents to P4
applied and regardless of reaction conditions, although the
utilization of bulky substituent can lead to phosphorus rich
compounds.[6, 7] We envision that the reaction of organodilithium reagents, for example, 1,4-dilithio-1,3-butadienes,
which have a dilithium bridge,[8] with P4 might yield interesting compounds because cooperative nucleophilic attack of
two Csp2¢Li bonds on P4 could selectively trap one phosphorus atom. Herein, we report a straightforward synthesis of
phospholyl lithium compounds from P4 and 1,4-dilithio-1,3butadienes. Phospholyl ligands have played a vital role in
coordination chemistry and organometallic chemistry
because they can stabilize various metals in common oxidation states or low oxidation states.[9, 10] This preparative
method for phospholyl lithiums has the following advantages:
step-economy, mild conditions, facile isolation, and excellent
yields based on the dilithium reagents.
Initially, we attempted a 1:1 molar ratio reaction between
dilithium reagent 1 a and P4 in THF. When a THF solution of
1 a was added to a THF solution of P4, a large amount of
yellow-brown solid formed immediately to give a suspension.
The suspension was stirred overnight and the solution turned
clear with a dark brown solid on the wall of the flask. The
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9187
Communications
Angewandte
Chemie
solution was then decanted to another flask. After removing
the solvent under reduced pressure, product 2 a could be
obtained quantitatively. Single crystals of 2 a were obtained
from a THF/hexane solution of 2 a. X-ray analysis of 2 a
revealed that it is a phospholyl lithium in which the lithium
atom is coordinated by a phospholyl in h5 mode and two THF
molecules in k1 mode (Figure 1).
Figure 1. Molecular structure of 2 a. All hydrogen atoms are omitted
for clarity, and ellipsoids are shown at 30 % probability. One carbon of
THF is disordered.
Dilithium reagents bearing different substituents[8d] can be
applied in the presented reaction (Scheme 2). When 1,4bis(trimethylsilyl)-2,3-dimethyl-1,4-dilithiobutadiene
(1 b)
was applied as the starting material, the corresponding 2 b
could be obtained quantitatively. In addition to a-trimethylsilyl-substituted dilithium reagents, the reaction of tetraalkylsubstituted dilithium reagents, for example, 1,2,3,4-tetraethyl1,4-dilithiobutadiene (1 c), with P4 led to quantitative production of the corresponding product 2 c. Interestingly, 2,3dibutyl-1,4-dilithiobutadiene (1 d) was also applied in this
reaction and quantitatively afforded the disubstituted phospholyl lithium 2 d. Furthermore, the styrene-type dilithium
reagent 1 e was reacted with P4 to give the phosphindolyl
lithium 2 e. Another styrene-type dilithium reagent, 1 f, which
can be easily prepared from nBuLi and diphenylacetylene in
TMEDA,[8e] also gave the corresponding product 2 f in 85 %
yield under the presented conditions.
This reaction could also be carried out on a preparative
scale, thereby demonstrating its practical usefulness
(Scheme 3).
Despite the fact that phospholyl lithiums can be obtained
through several known routes,[9, 10e, 11] practical routes to
obtain phospholyl lithiums require at least three steps from
the starting P4 : 1) the chlorination of P4 to afford PCl3 ; 2) the
synthesis of phospholes; and 3) cleavage of the P¢C/P¢Cl
bond of phospholes. These multistep synthetic routes to
phospholyl lithiums are both time-consuming and costintensive owing to the numerous reactions and corresponding
isolations. However, the development of new synthetic
methods to phospholyl lithium has been very limited over
the past century, with the exception of the recent work of
9188
www.angewandte.org
Scheme 2. One-step synthesis of phospholyl lithiums.
Scheme 3. Synthesis of 2 b on a preparative scale.
Duan and co-workers.[12] The present method enables the
practical, highly efficient, and convenient preparation of
differently substituted phospholyl lithiums.
The interesting and novel results of the work reported
herein prompted us to ponder why the reaction of 1,4-dilithio1,3-butadienes with P4 can yield cleanly phospholyl lithiums.
To gain some mechanistic information, different ratios of 1,4dilithio-1,3-butadienes to P4 were tested. When the number of
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 9187 –9190
Angewandte
Communications
equivalents of P4 was increased to 1.5, similar results to those
with 1.0 equiv can be obtained. However, when the number of
equivalents of P4 was decreased to 0.5 or 0.25, only a mixture
could be obtained. These results clearly show that the reaction
requires at least 1.0 equiv of P4. However, only one phosphorus atom is incorporated into a phospholyl lithium. Thus,
three phosphorus atoms may be released as a structurally
unknown insoluble polyphosphide [LiP3]n.
Based on this information, we proposed a mechanism
involving the butterfly-like P4 intermediate IM1’, which is
widely observed in some processes involving aryl lithium
reagents (see Scheme S1 in the Supporting Information).[3d, 7a]
To gain more insight into this reaction, DFT calculations were
carried out with Gaussian 09. All of the intermediates and
transition states were fully optimized at the B3LYP level
using the 6-31 + G(d) basis set in the gas phase. However, the
DFT calculations do not support the existence of IM1’’ in the
present process (Scheme 4 and Figure 2). From the calculation result, the first step is the coordination of P4 to one
lithium of 1,4-dilithio-1,3-butadiene, affording the intermediate IM1. The transformation of IM1 into IM2 then takes place
in a single step, in which two P¢P bonds are cleaved
simultaneously with the concomitant formation of two new
P¢Li bonds and a P¢C bond. The barrier to the transition
state TS1 is 24.7 kcal mol¢1 in the gas phase, and only
Chemie
9.6 kcal mol¢1 in THF. Thus, the process from IM1 to IM2
can be viewed as the cooperative insertion of one P atom into
one head of the C2¢Li2 bridge. This step is in strong contrast to
the well-known mechanism of stepwise P¢P bond cleavage in
the reaction of P4 with nucleophilic reagents. Finally, C¢P
bond coupling via the cyclization transition state TS2 affords
2 c with the release of [LiP3]n.
In summary, we have developed a method to access
phospholyl lithiums directly from P4 and 1,4-dilithio-1,3butadienes through a cooperative nucleophilic attack of two
Csp2¢Li bonds on P4. A broad range of di- or tetrasubstituted
phospholyl lithium reagents bearing different alkyl, aryl, or
silyl groups can be prepared conveniently and efficiently. In
addition, a novel cooperative insertion mechanism in the
reaction of P4 with 1,4-dilithio-1,3-dienes is proposed and was
confirmed by DFT calculations. This understanding of the
process will open new opportunities for the design of
straightforward syntheses of organophosphorus compounds
from P4.
Acknowledgements
This work was supported by the “973” program from National
Basic Research Program of China (2012CB821600) and
Natural Science Foundation of China (nos. 21572005,
21372014).
Keywords: C¢P coupling · P4 functionalization ·
phospholyl lithium · phosphorus · synthetic methods
How to cite: Angew. Chem. Int. Ed. 2016, 55, 9187 – 9190
Angew. Chem. 2016, 128, 9333 – 9336
Scheme 4. DFT-calculated potential-energy surfaces of the reaction
between 1 c and P4.
Figure 2. Optimized structures of TS1, IM2, and TS2. Selected bond
lengths (ç) of TS1: C1¢Li1 2.056, C4¢Li1 2.545, P1¢Li1 2.242, C4¢P1
2.201, P1¢P2 2.297, P1¢P3 2.643. Selected bond lengths (ç) of IM2:
C1¢Li1 2.094, C1¢Li2 2.021, P1¢Li1 2.370, P1¢Li2 2.561, P2¢Li1 2.861.
Selected bond lengths (ç) of TS2: C1¢Li1 2.172, C1¢P1 2.359, P1¢Li1
2.374, P2¢Li1 2.588, P1¢P4 2.454, P2¢P4 2.276.
Angew. Chem. Int. Ed. 2016, 55, 9187 –9190
[1] J. Emsley in The 13th Element: The Sordid Tale of Murder, Fire,
and Phosphorus, Wiley, New York, 2000.
[2] a) D. E. C. Corbridge in Phosphorus 2000. Chemistry, biochemistry & technology, Elsevier, Amsterdam, 2000; b) R. Engel in
Synthesis of Carbon-Phosphorus Bonds, 2nd ed., CRC, Boca
Raton, 2004; c) J.-L. Montchamp, Acc. Chem. Res. 2014, 47, 77 –
87; d) J. M. Lynam, Angew. Chem. Int. Ed. 2008, 47, 831 – 833;
Angew. Chem. 2008, 120, 843 – 845.
[3] Selected reviews of P4 activation: a) S. Khan, S. S. Sen, H. W.
Roesky, Chem. Commun. 2012, 48, 2169 – 2179; b) N. A. Giffin,
J. D. Masuda, Coord. Chem. Rev. 2011, 255, 1342 – 1359; c) B. M.
Cossairt, N. A. Piro, C. C. Cummins, Chem. Rev. 2010, 110,
4164 – 4177; d) M. Caporali, L. Gonsalvi, A. Rossin, M. Peruzzini, Chem. Rev. 2010, 110, 4178 – 4235; e) M. Scheer, G. Bal‚zs,
A. Seitz, Chem. Rev. 2010, 110, 4236 – 4256.
[4] Selected examples of metal-mediated P4 activation: a) B. Pinter,
K. T. Smith, M. Kamitani, E. M. Zolnhofer, B. L. Tran, S. Fortier,
M. Pink, G. Wu, B. C. Manor, K. Meyer, M.-H. Baik, D. J.
Mindiola, J. Am. Chem. Soc. 2015, 137, 15247 – 15261; b) S. Yao,
N. Lindenmaier, Y. Xiong, S. Inoue, T. Szilv‚si, M. Adelhardt, J.
Sutter, K. Meyer, M. Driess, Angew. Chem. Int. Ed. 2015, 54,
1250 – 1254; Angew. Chem. 2015, 127, 1266 – 1270; c) C. Camp,
L. Maron, R. G. Bergman, J. Arnold, J. Am. Chem. Soc. 2014,
136, 17652 – 17661; d) C. C. Cummins, C. Huang, T. J. Miller,
M. W. Reintinger, J. M. Stauber, I. Tannou, D. Tofan, A.
Toubaei, A. Velian, G. Wu, Inorg. Chem. 2014, 53, 3678 – 3687;
e) D. Patel, F. Tuna, E. J. L. McInnes, W. Lewis, A. J. Blake, S. T.
Liddle, Angew. Chem. Int. Ed. 2013, 52, 13334 – 13337; Angew.
Chem. 2013, 125, 13576 – 13579; f) C. D. Martin, C. M. Wein-
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
9189
Communications
[5]
[6]
[7]
[8]
9190
stein, C. E. Moore, A. L. Rheingold, G. Bertrand, Chem.
Commun. 2013, 49, 4486 – 4488; g) W. Huang, P. L. Diaconescu,
Chem. Commun. 2012, 48, 2216 – 2218; h) M. D. Walter, J.
Grunenberg, P. S. White, Chem. Sci. 2011, 2, 2120 – 2130; i) M.
Demange, X.-F. Le Goff, P. Le Floch, N. M¦zailles, Chem. Eur. J.
2010, 16, 12064 – 12068.
Selected reviews of C¢P bond formation from activated P4 :
a) M. Serrano-Ruiz, A. Romerosa, P. Lorenzo-Luis, Eur. J.
Inorg. Chem. 2014, 1587 – 1598; b) Y. G. Budnikova, D. I.
Tazeev, T. V. Gryaznova, O. G. Sinyashin, Russ. J. Electrochem.
2006, 42, 1127 – 1133; c) M. Peruzzini, L. Gonsalvi, A. Romerosa, Chem. Soc. Rev. 2005, 34, 1038 – 1047.
a) B. A. Trofimov, L. Brandsma, S. N. Arbuzova, N. K. Gusarova, Russ. Chem. Bull. 1997, 46, 849 – 850; b) R. Riedel, H.-D.
Hausen, E. Fluck, Angew. Chem. Int. Ed. Engl. 1985, 24, 1056 –
1057; Angew. Chem. 1985, 97, 1050 – 1050; c) M. M. Rauhut,
A. M. Semsel, J. Org. Chem. 1963, 28, 473 – 477.
a) J. E. Borger, A. W. Ehlers, M. Lutz, J. C. Slootweg, K.
Lammertsma, Angew. Chem. Int. Ed. 2016, 55, 613 – 617;
Angew. Chem. 2016, 128, 623 – 627; b) A. Hîbner, T. Bernert,
I. S•nger, E. Alig, M. Bolte, L. Fink, M. Wagner, H.-W. Lerner,
Dalton Trans. 2010, 39, 7528 – 7553; c) C. Charrier, N. Maigrot, L.
Ricard, P. Le Floch, F. Mathey, Angew. Chem. Int. Ed. Engl.
1996, 35, 2133 – 2134; Angew. Chem. 1996, 108, 2282 – 2283.
Organodilithium reagents: a) S. Zhang, W.-X. Zhang, Z. Xi, Top.
Organomet. Chem. 2014, 47, 1 – 42; b) W.-X. Zhang, Z. Xi, Org.
Chem. Front. 2014, 1, 1132 – 1139; c) T. Kuwabara, J.-D. Guo, S.
Nagase, M. Minoura, R. H. Herber, M. Saito, Organometallics
2014, 33, 2910 – 2913; d) Z. Xi, Acc. Chem. Res. 2010, 43, 1342 –
www.angewandte.org
[9]
[10]
[11]
[12]
Angewandte
Chemie
1351; e) W. Bauer, M. Feigel, G. Mîller, P. v. R. Schleyer, J. Am.
Chem. Soc. 1988, 110, 6033.
Selected reviews of phospholide anions: a) L. Nyul‚szi, Chem.
Rev. 2001, 101, 1229 – 1246; b) F. Mathey, Coord. Chem. Rev.
1994, 137, 1 – 52; c) F. Mathey, J. Organomet. Chem. 1994, 475,
25 – 30; d) F. Mathey, Chem. Rev. 1988, 88, 429 – 453.
Selected examples of phospholide anions: a) M. Ogasawara, M.
Shintani, S. Watanabe, T. Sakamoto, K. Nakajima, T. Takahashi,
Organometallics 2011, 30, 1487 – 1492; b) A. Glçckner, T.
Bannenberg, S. Bîschel, C. G. Daniliuc, P. G. Jones, M. Tamm,
Chem. Eur. J. 2011, 17, 6118 – 6128; c) F. Jaroschik, T. Shima, X.
Li, K. Mori, L. Ricard, X.-F. Le Goff, F. Nief, Z. Hou, Organometallics 2007, 26, 5654 – 5660; d) F. Nief, D. Turcitu, L. Ricard,
Chem. Commun. 2002, 1646 – 1647; e) M. Westerhausen, M. H.
Digeser, H. Nçth, W. Ponikwar, T. Seifert, K. Polborn, Inorg.
Chem. 1999, 38, 3207 – 3214.
a) D. Gudat, V. Bajorat, S. H•p, M. Nieger, G. Schrçder, Eur. J.
Inorg. Chem. 1999, 1169 – 1174; b) S. Holand, M. Jeanjean, F.
Mathey, Angew. Chem. Int. Ed. Engl. 1997, 36, 98 – 100; Angew.
Chem. 1997, 109, 117 – 119; c) E. Niecke, M. Nieger, P. Wenderoth, Angew. Chem. Int. Ed. Engl. 1994, 33, 353 – 354; Angew.
Chem. 1994, 106, 362 – 363; d) T. Douglas, K. H. Theopold,
Angew. Chem. Int. Ed. Engl. 1989, 28, 1367 – 1368; Angew.
Chem. 1989, 101, 1394 – 1395.
Y. Xu, Z. Wang, Z. Gan, Q. Xi, Z. Duan, F. Mathey, Org. Lett.
2015, 17, 1732 – 1734.
Received: March 20, 2016
Published online: June 15, 2016
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 9187 –9190